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Calcium‐Mediated Dearomatization, CH Bond Activation, and Allylation of Alkylated and Benzannulated Pyridine Derivatives
Author(s) -
Jochmann Phillip,
Leich Valeri,
Spaniol Thomas P.,
Okuda Jun
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201101489
Subject(s) - chemistry , pyridine , medicinal chemistry , quinoline , isoquinoline , steric effects , stereochemistry , alkylation , yield (engineering) , organic chemistry , catalysis , materials science , metallurgy
A facile and general synthetic pathway for the production of dearomatized, allylated, and CH bond activated pyridine derivatives is presented. Reaction of the corresponding derivative with the previously reported reagent bis(allyl)calcium, [Ca(C 3 H 5 ) 2 ] ( 1 ), cleanly affords the product in high yield. The range of N‐heterocyclic compounds studied comprised 2‐picoline ( 2 ), 4‐picoline ( 3 ), 2,6‐lutidine ( 4 ), 4‐ tert ‐butylpyridine ( 5 ), 2,2′‐bipyridine ( 6 ), acridine ( 7 ), quinoline ( 8 ), and isoquinoline ( 9 ). Depending on the substitution pattern of the pyridine derivative, either carbometalation or CH bond activation products are obtained. In the absence of methyl groups ortho or para to the nitrogen atom, carbometalation leads to dearomatized products. C(sp 3 )H bond activation occurs at ortho and para situated methyl groups. Steric shielding of the 4‐position in pyridine yields the ring‐metalated product through C(sp 2 )H bond activation instead. The isolated compounds [Ca(2‐CH 2 ‐C 5 H 4 N) 2 (THF)] ( 2 b ⋅(THF)), [Ca(4‐CH 2 ‐C 5 H 4 N) 2 (THF) 2 ] ( 3 b ⋅(THF) 2 ), [Ca(2‐CH 2 ‐C 5 H 3 N‐6‐CH 3 ) 2 (THF) n ] ( 4 b ⋅(THF) n ; n =0, 0.75), [Ca{2‐C 5 H 3 N‐4‐C(CH 3 ) 3 } 2 (THF) 2 ] ( 5 c ⋅(THF) 2 ), [Ca{4,4′‐(C 3 H 5 ) 2 ‐(C 10 H 8 N 2 )}(THF)] ( 6 a ⋅(THF)), [Ca(NC 13 H 9 ‐9‐C 3 H 5 ) 2 (THF)] ( 7 a ⋅(THF)), [Ca(4‐C 3 H 5 ‐C 9 H 7 N) 2 (THF)] ( 8 b ⋅(THF)), and [Ca(1‐C 3 H 5 ‐C 9 H 7 N) 2 (THF) 3 ] ( 9 a ⋅(THF) 3 ) have been characterized by NMR spectroscopy and metal analysis. 9 a ⋅(THF) 4 and 4 b ⋅(THF) 3 were additionally characterized in the solid state by X‐ray diffraction experiments. 4 b ⋅(THF) 3 shows an aza‐allyl coordination mode in the solid state. Based on the results, mechanistic aspects are discussed in the context of previous findings.